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Reprogramming the immunological microenvironment through radiation and targeting Axl NATURE COMMUNICATIONS Aguilera, T. A., Rafat, M., Castellini, L., Shehade, H., Kariolis, M. S., Hui, A. B., Stehr, H., von Eyben, R., Jiang, D., Ellies, L. G., Koong, A. C., Diehn, M., Rankin, E. B., Graves, E. E., Giaccia, A. J. 2016; 7

Abstract

Increasing evidence suggests that ionizing radiation therapy (RT) in combination with checkpoint immunotherapy is highly effective in treating a subset of cancers. To better understand the limited responses to this combination we analysed the genetic, microenvironmental, and immune factors in tumours derived from a transgenic breast cancer model. We identified two tumours with similar growth characteristics but different RT responses primarily due to an antitumour immune response. The combination of RT and checkpoint immunotherapy resulted in cures in the responsive but not the unresponsive tumours. Profiling the tumours revealed that the Axl receptor tyrosine kinase is overexpressed in the unresponsive tumours, and Axl knockout resulted in slower growth and increased radiosensitivity. These changes were associated with a CD8(+) T-cell response, which was improved in combination with checkpoint immunotherapy. These results suggest a novel role for Axl in suppressing antigen presentation through MHCI, and enhancing cytokine release, which promotes a suppressive myeloid microenvironment.

View details for DOI 10.1038/ncomms13898

View details for Web of Science ID 000390399500001

View details for PubMedID 28008921

View details for PubMedCentralID PMC5196438